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Cancer Cell. 2008 Mar;13(3):193-205. doi: 10.1016/j.ccr.2007.11.032.

Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells.

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  • 1Division of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, 269 Campus Drive, CCSR-South, Room 1255, Stanford, CA 94305, USA.


Tumor vasculature is derived from sprouting of local vessels (angiogenesis) and bone marrow (BM)-derived circulating cells (vasculogenesis). By using a model system of transplanting tumors into an irradiated normal tissue to prevent angiogenesis, we found that tumors were unable to grow in matrix metalloproteinase-9 (MMP-9) knockout mice, but tumor growth could be restored by transplantation of wild-type BM. Endothelial progenitor cells did not contribute significantly to this process. Rather, CD11b-positive myelomonocytic cells from the transplanted BM were responsible for tumor growth and the development of immature blood vessels in MMP-9 knockout mice receiving wild-type BM. Our results suggest that MMP-9 could be an important target for adjunct therapy to enhance the response of tumors to radiotherapy.

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